Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells

Cancer Lett. 2014 Mar 28;344(2):195-203. doi: 10.1016/j.canlet.2013.10.031. Epub 2013 Nov 6.

Abstract

MicroRNA-449a (miR-449a) was significantly downregulated in 156 lung cancer tissues (p<0.001). We found that the low expression of miR-449a was highly correlated with cancer recurrence and survival of lung cancer patients. The transient introduction of miR-449a caused cell cycle arrest and cell senescence in A549 and 95D cells. Further studies revealed that E2F3 was a direct target of miR-449a in lung cancer cells. miR-449a also suppressed tumor formation in vivo in nude mice. These results suggest that miR-449a plays an important role in lung cancer tumorigenesis and that miR-449a might predict cancer recurrence and survival of lung cancer patients.

Keywords: E2F3; Lung cancer; Senescence; Survival; miR-449a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cellular Senescence / genetics
  • E2F3 Transcription Factor / genetics*
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • E2F3 Transcription Factor
  • E2F3 protein, human
  • MIRN449 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering